tacrolimus and Keloid

A broad range of therapeutics is currently available for the treatment of keloids, but none have been shown to be completely effective in flattening existing keloids, reducing associated symptoms or preventing recurrence. Therefore, newer treatments not routinely used for keloids have been examined more recently, including laser therapy, intralesional interferon and imiquimod, which have had variable success as therapies for keloids. This article briefly reviews such experimental data and presents recommendations for management of keloids as well.

Topics: Adrenal Cortex Hormones; Aminoquinolines; Chemotherapy, Adjuvant; Humans; Imiquimod; Immunosuppressive Agents; Interferon alpha-2; Interferon Inducers; Interferon-alpha; Keloid; Laser Therapy; Recombinant Proteins; Tacrolimus

The purpose of this study was to investigate the effects of tacrolimus on human fibroblasts derived from unwounded skin, hypertrophic scars (HTS), and keloids. We hypothesized that tacrolimus, a potent anti-inflammatory and immunosuppressant drug known to attenuate solid organ transplant fibrosis, would block collagen expression in human dermal fibroblasts.. We performed genomewide microarray analysis on human dermal fibroblasts treated with tacrolimus in vitro. We used principal component analysis and hierarchical clustering to identify targets regulated by tacrolimus. We performed quantitative polymerase chain reaction to validate the effect of tacrolimus on collagen 1 and 3 expression.. We identified 62, 136, and 185 gene probes on microarray analysis that were significantly regulated (P < 0.05) by tacrolimus in normal, HTS, and keloid fibroblasts, respectively. Collagen pathways were not blocked after tacrolimus exposure in any of the fibroblast groups; we validated these findings using quantitative polymerase chain reaction for collagen 1 and 3. Microarray gene expression of NME/NM23 nucleoside diphosphate kinase 1 and heterogeneous nuclear ribonucleoprotein H3-2H9 were significantly downregulated (P < 0.05) by tacrolimus in both HTS and keloid fibroblast populations but not normal fibroblasts.. Tacrolimus does not modulate the expression of collagen 1 or 3 in human dermal fibroblasts in vitro. Microarray gene expression of NME/NM23 nucleoside diphosphate kinase 1 and heterogeneous nuclear ribonucleoprotein H3-2H9 are blocked by tacrolimus in pathologic fibroblasts but not normal fibroblasts, and may represent novel genes underlying HTS and keloid pathogenesis. Tacrolimus-based anti-fibrotics might prove more effective if non-fibroblast populations such as inflammatory cells and keratinocytes are targeted.

Topics: Cells, Cultured; Cicatrix, Hypertrophic; Collagen; Fibroblasts; Gene Expression; Genome-Wide Association Study; Humans; Immunosuppressive Agents; Keloid; Oligonucleotide Array Sequence Analysis; Principal Component Analysis; Skin; Tacrolimus; Wound Healing

  Keloid is a unique proliferative disorder of fibroblasts resulting from derailment of the typical wound healing process. Due to lack of animal models for therapeutic testing, treatment of keloids remains a clinical challenge. Transforming growth factor (TGF)-β1-related signalling plays a key role in keloid formation. As tacrolimus (FK506) has been reported to inhibit the effects of TGF-β1 on cultured fibroblasts, we hypothesized that FK506 may be useful in treating keloids.. To explore the effects of FK506 on TGF-β1-stimulated keloid fibroblasts (KFs) in terms of proliferation, migration and collagen production and to investigate the regulatory pathways involved.. Fibroblasts derived from keloids were treated with TGF-β1 with or without FK506. Relevant assays including 5-bromo-2'-deoxyuridine incorporation assay, in vitro scratch assay, reverse transcription-polymerase chain reaction (PCR), quantitative PCR and Western blotting were performed.. The proliferation and migration of KFs were significantly higher than those of normal fibroblasts. FK506 markedly inhibited KF proliferation, migration and collagen production enhanced by TGF-β1. The increase in TGF-β receptor I and II expression in TGF-β1-treated KFs was suppressed by FK506 treatment. TGF-β1 increased the phosphorylation of Smad2/3 and Smad4 in KFs, and this enhancing effect was abrogated by FK506. In addition, FK506 significantly increased the expression of Smad7 which was suppressed by TGF-β1 treatment.. Our results demonstrate that FK506 effectively blocks the TGF-β/Smad signalling pathway in KFs by downregulation of TGF-β receptors and suggest that FK506 may be included in the armamentarium for treating keloids.

Topics: Adult; Cell Movement; Cell Proliferation; Cells, Cultured; Collagen; Down-Regulation; Female; Fibroblasts; Humans; Immunosuppressive Agents; Keloid; Receptors, Transforming Growth Factor beta; Signal Transduction; Smad Proteins; Tacrolimus; Transforming Growth Factor beta

Keloids and hypertrophic scars (HSc) affect 4.5-16% of the population. Thus far, the different approaches of keloid treatment are not very efficient, with a 50% relapse rate and many ongoing researches are looking for simple, safe and more efficient therapeutic methods. Tacrolimus is an immunomodulator that could be useful in treating keloid.. The objective of this study is to evaluate the effectiveness of Tacrolimus in inhibiting HSc formation on rabbits' ears model and to check optical skin spectroscopy in tissue characterization.. Our study was carried out on 20 New-Zealand female white rabbits. HSc were obtained by wounding rabbits' ear. These wounds were treated with intradermal injections of tacrolimus (0.2-0.5 mg/cm(2)) or a vehicule. The assessment of treatment efficacy was performed by clinical examinations, histological assay and skin spectrometry.. Tacrolimus did not induce general or local side-effects. The scar elevation index in treated subjects was half less than that of the untreated ones. Furthermore, dermal thickness and inflammatory cellular density were both significantly smaller for treated scars than for the control ones. In vivo optical skin spectroscopy can characterize hypertrophic and normal skin with high sensibility and specificity.. Intradermal injection of tacrolimus at 0.5 mg/cm(2) is an efficient way to prevent HSc in our experiment model and its tolerance is correct. Optical spectroscopy could be a good non-invasive tool to evaluate HSc treatment. These promising results might be proposed for patients suffering from keloid.

Topics: Animals; Cicatrix, Hypertrophic; Dermoscopy; Disease Models, Animal; Ear, External; Female; Hypertrophy; Immunosuppressive Agents; Injections, Intradermal; Keloid; Rabbits; Spectrum Analysis; Tacrolimus; Wounds and Injuries